The long term objectives of the Periodontal Disease Research Center are: a) to identify groups of individuals who are at high risk for development of periodontal disease because of smoking, diabetes, stress/distress, and coping behaviors; b) to develop molecular approaches to antiinfective and antiinflammatory therapy, and to diagnosis of high susceptibility states; and c) to assess the role of growth factors in regenerative therapy. Aims to achieve these objectives relate to four interdependent projects, two pilot studies, and a support core. Project 1, Risk Factors for Periodontal Disease, proposes longitudinal epidemiologic studies to evaluate the extent to which diabetes, smoking, stress/distress, and coping behaviors influence the incidence and rate of periodontal disease. The temporal sequence of infection, host response, and periodontal destruction, as well as acquisition and transmission of periodontopathic organisms will also be established in high risk individuals. Project 2, Molecular Basis of Periodontal Regeneration, is directed to developing molecular approaches to stimulate regeneration of periodontal tissues, while limiting ankylosis and root resorption. The role of epidermal growth factor receptors in periodontal ligament fibroblast differentiation will be assessed. Growth factors, retinoic acid and its derivatives, and bone morphogenic proteins will be evaluated for their influence on proliferation, migration, and differentiation of progenitor cells in vitro, animal model, and human studies. Project 3, IL-8 and Periodontal Diseases, will investigate the role of IL-8, a lymphokine proposed to be central to modulating periodontal infections. Understanding IL-8 receptor abnormalities which are found in juvenile periodontal disease may provide a marker for susceptibility. Structure/function relationships of IL-8 receptor will provide the basis for development of antiinflammatory antagonists. Project 4, Defensins, Bactenecins and Periodontal Diseases; proposes to evaluate these peptide antimicrobial agents from neutrophil granules. Their critical structure/function relationships will serve in the design of novel antibiotics. Coding sequences of these peptides are candidates for in vivo gene therapy experiments in salivary glands. Pilot Project 1, Neutrophil Function in Severe Periodontitis Patients, focuses on assessing how and to what extent neutrophils in high risk patients who are diabetic and/or smoke, are compromised. Pilot Project 2, In Vivo Gene Transfer Experiments in Rat Salivary Glands, is designed to develop adenovirus constructs with potential for in vivo gene transfer into salivary glands. Expression of genetically transferred antimicrobial and antiadherence products in saliva may interfere with development or progression of oral infections. The results of these integrated Center studies, combining molecular biological and population-based clinical studies will be applied to reduction of tooth loss, edentulousness, and periodontal disease in high risk populations and minorities; goals in concert with the objectives of "Healthy People: 2000."